Uric acid, the final product of purine catabolism, is physiologically excreted in the urine. the source of uric acid includes endogenous and exogenous, of which endogenous uric acid accounts for approximately 80%, while the remainder is derived from dietary purines. Thus, overproduction of uric acid or insufficient renal elimination can cause hyperuricemia, which is generally defined as a serum level of uric acid of >6.0 mg/dL. Hyperuricemia can be asymptomatic, but when the blood uric acid concentration exceeds 6.8 mg/dL without treatment, monosodium urate crystallizes and is deposited in joints or surrounding tissues. This is the cause of gout, a severe disease that affects millions of people, especially adult men, worldwide. Both hyperuricemia and gout are associated with a range of chronic diseases, including hypertension, diabetes mellitus, metabolic syndrome, and renal and cardiovascular diseases.
Currently, there are several drug strategies to control urate levels. For a long time, the preferred drugs for clinical treatment of hyperuricemia were xanthine oxidase (XO) inhibitors. However, an appreciable proportion of patients do not respond well to XO inhibitors, due to serious side effects and the development of resistance. Thus, uricosuric drugs, which increase the urinary excretion of uric acid, are another option for patients who are intolerant of XO inhibitors.
Lesinuard is a new drug used for the treatment of gout. It was discovered fortuitously by Ardea Biosciences in 2008. Lesinurad was approved on 22 Dec. 2015 by US FDA, and was noted to increase the excretion of uric acid by inhibiting the uric acid salt transport protein 1 (URAT1).
On the other hand, lesinurad is associated with adverse events, such as headache and increased blood creatinine. Also, lesinurad should be used with caution in patients with liver and kidney insufficiency and cardiovascular disease. Therefore, there is still a need for better inhibitors targeting URAT1.
